JP2005521527A - Methods and devices for delivering substances into the skin - Google Patents

Abstract

A device (10) for delivering a substance into a patient's skin comprising a body (12) and a skin penetration device (14) having a skin penetration member such as at least one microneedle. The body (12) includes an internal cavity (22) and a device (48, 92, 148, 156) that indicates that a sufficient amount of material has been delivered to the patient and generates supply pressure to deliver material from the cavity. ). This display device is visible from the outside of the supply device. In some embodiments, the display device is an inflatable diaphragm that is elastic and generates a supply pressure when the cavity is filled with material.

Description

  The present invention relates to a method and device for delivering a substance into a patient's skin. The present invention also relates to a microneedle delivery device that contains a unit dose of substance and supplies it intradermally to a patient.

  Subcutaneous delivery devices using cannulas are useful for many applications. However, since pain is usually caused by a cannula, development of delivery methods with less pain has been underway. Recently, many intradermal delivery devices that employ microneedles have been designed. The length of the microneedle is chosen so that it penetrates the skin to the depth that the drug or drug is delivered to the patient.

  In humans, the skin consists of several layers, and the upper composite layer constitutes the epithelial layer. The outermost layer of the skin, that is, the stratum corneum, has a well-known barrier property, and prevents fine particles and various substances from entering the body and body fluids from coming out of the body. See Non-Patent Document 1.

  The stratum corneum is a complex structure of compacted keratinized cell remnant having a thickness of about 10-30 microns, forming a water-resistant thin film, And prevents various compounds from leaving the body.

  The natural impermeability of the stratum corneum prevents most drugs and other substances from being administered through the skin. Various methods and devices have been proposed for increasing the permeability of the skin and diffusing various drugs for use in the body through the skin. Typically, it increases the permeability of the skin or the power and energy used to treat through the skin, making it easier to deliver the drug through the skin. See Non-Patent Document 1.

  Another method of supplying various substances through the skin is performed by forming fine pores and cuts through the stratum corneum. Many drugs can be efficiently administered by penetrating or penetrating the stratum corneum and supplying the drug to the skin in or below the stratum corneum. Devices for puncturing the stratum corneum generally comprise a plurality of micron-sized needles and blades having a length selected to puncture the stratum corneum without completely penetrating the epithelium. . Examples of these devices are disclosed in Patent Document 1 by Godshall et al., Patent Document 2 by Lee et al. And Patent Document 3.

  The aforementioned devices with micron-sized needles and blades supply substances to the body by flowing the substances through the holes and channels of the devices. Many of these conventional devices are unable to provide a controlled delivery of material to the patient.

  These conventional methods and devices for intradermal administration of substances have not been successful. Thus, there continues to be a need for improved devices for administering various drugs and other substances to the body.

US Pat. No. 5,879,326 US Pat. No. 5,250,023 International Publication No. 97/48440 Bouwstra, et al., (2001) Skin Pjarmacol Appl Skin Physiol, 14 Suppl 1: 52-62 Moriello, K.A .; Mason, I.S., Handbook of Small Animal Dermatology, Pergamon, 1995, pp. 19-44

  The present invention relates to a method and device for delivering a substance through a patient's skin. More particularly, the present invention relates to a method and device for delivering drugs such as drugs and vaccines under the stratum corneum of skin to the depth at which the drugs are absorbed and utilized by the body. Furthermore, the present invention relates to a method of manufacturing and assembling a device that supplies substances intradermally through a patient's skin.

  Accordingly, it is a primary object of the present invention to provide a low profile device that reduces the level of discomfort imparted to a patient, the device having a skin penetrating member that introduces a substance into the patient.

  It is a further object of the present invention to provide a device that penetrates the skin to deliver a unit dose of substance without causing substantial pain to the patient.

  Another object of the present invention is to provide at least one fine skin penetrator (eg, microtube, microneedle, microblade or lancet) for delivering substance to the patient through the stratum corneum of the skin. It is to provide a device having the above.

  It is a further object of the present invention to provide a delivery device having at least one skin penetrating member and a chamber containing a substance to be delivered to a patient.

  Yet another object of the present invention is to provide indicator means for indicating that a sufficient amount of a substance, such as a pre-weighed drug, has been delivered from the chamber into the patient's skin, and for administering the administration into the chamber during the administration operation. It is to provide an intradermal delivery device having a mechanism for generating a pressure to promote.

  Another object of the present invention is a device for supplying a substance to a patient, which has a support part with an internal supply channel having a very small volume, and is joined to the support part so that a fluid is supplied to the supply channel. It is an object of the present invention to provide a device having a micro skin-penetrating device that communicates with a patient and supplies substances to a patient.

  It is a further object of the present invention to provide a delivery device having a plurality of microscopic skin penetrating members that generate a delivery facilitating pressure in an internal channel containing a substance for delivery to a patient, and that a sufficient quantity of the substance is present. The object is to provide a device with at least one elastic wall to indicate when it has been administered.

  Another object of the present invention is to provide an intradermal delivery device having an internal chamber having a mechanism for filling and pressurizing the internal chamber.

  Another object of the present invention is to provide a liquid source for supplying liquid material to an internal cavity by a force that sufficiently pressurizes the housing during a supply operation and generates a supply promoting pressure for an intradermal supply device. It is to provide.

  Yet another object of the present invention is to provide a substance into a patient's skin comprising providing a delivery device having a housing having an internal cavity and at least one skin penetration device in fluid communication with the cavity. The housing is pressurizable to maintain a supply facilitating pressure in the cavity, and the supply device is positioned in a target area of the patient's skin and applied with sufficient force. And is configured to pierce the skin of the patient. A material is introduced into the cavity of the housing, which generates a supply facilitating pressure within the cavity.

  These and other objects of the present invention include a housing having an internal cavity sized to receive a substance to be delivered to a patient, a skin penetration device in fluid communication with the cavity, and in fluid communication with the cavity. This is substantially achieved by providing an intradermal delivery device comprising an elastically biased movable member. This elastically biased movable member generates a supply facilitating pressure within the cavity to deliver material from the cavity to the skin penetrating member and indicates that a sufficient amount of material has been delivered to the patient. .

  An object and advantage of the present invention is that it is made of an inflatable material with sufficient elasticity that generates a supply facilitating pressure when the cavity is filled with a substance and indicates that the cavity has not yet supplied a sufficient quantity of substance. Further achieved by providing an intradermal delivery device comprising a housing having at least one portion formed. A skin penetration device is coupled to the housing and is in fluid communication with the cavity.

  The present invention relates to a device for delivering a substance into a patient's skin. More particularly, the invention relates to an intradermal delivery device and method that administers a substance beneath the stratum corneum of a patient's skin where it is absorbed and utilized by the body.

  As used herein, the term “penetrate” means entering a target such as a skin layer without completely passing through it. The term “pierce” means completely passing through an object such as a skin layer.

  These devices and methods of the present invention are suitable for use in administering various substances, such as drugs, to a patient, particularly a human patient. As used herein, the term “pharmaceutical agent” includes substances having biological activity that can be delivered through body membranes and surfaces, especially through the skin. Examples of the drug include antibiotics, antiviral agents, analgesics, anesthetics, appetite suppressants, anti-arthritis agents, antidepressants, antihistamines, anti-inflammatory agents, antitumor agents, vaccines including DNA vaccines, etc. . Other substances that can be delivered into the patient's skin can include proteins, peptides and fragments thereof. Proteins and peptides can be natural, synthesized or recombinantly produced.

  The delivery device of the present invention is configured to penetrate a selected layer of the patient's dermis to obtain the desired penetration depth. The desired penetration depth is determined by the material to be delivered and the desired absorption rate by the body. If there is little penetration, the substance will be absorbed quickly by the body, and if there is much penetration, the supply will be slow. The skin penetrating member is adapted to have a length of about 50 microns to 1500 microns. An arrangement of skin penetrating members can also be used. The penetrating member is configured to penetrate the stratum corneum without hitting the nerve edge and causing pain. By supplying the substance under the stratum corneum, the substance is absorbed and utilized by the body without substantially causing pain or discomfort to the patient. Preferably, the skin penetrating member has a depth and diameter that penetrates the skin to the extent that the patient feels little or no pain, for example, below the stratum corneum and above the nerve edges.

  The present invention relates to an intradermal delivery device for delivering a substance into a patient's skin, wherein the device can maintain a delivery promoting pressure for delivering the substance. More particularly, the present invention relates to a unit dose drug delivery device that continuously delivers a substance through a patient's skin.

  Objects, advantages, and other salient features of the present invention will become apparent by reference to the following description of the preferred embodiments of the invention and the accompanying drawings.

  As can be seen from FIGS. 1 to 6, the first embodiment of the delivery device of the present invention indicated by reference numeral 10 comprises a housing 12 and a skin penetration device 14. The housing 12 is sized to removably attach to the surface of the skin for containing the substance to be delivered to the patient. The skin penetration device 14 is combined with the housing 12 and penetrates the patient's skin, through which material is delivered from the housing 12 through the skin. The present invention is used for the application of therapeutic agents across the stratum corneum for both humans and animals. For example, dermatology in dogs and cats is similar to human dermatology in terms of stratum corneum location and permeability. See Non-Patent Document 2.

  The housing 12 is substantially circular with a top wall 16, a bottom wall 18, and a side wall 20 extending between the top wall 16 and the bottom wall 18. The top wall 16, the bottom wall 18 and the side wall 20 form an internal cavity 20 as shown in FIGS. 5 and 6.

  The bottom wall 18 is substantially flat, part of which is formed by the skin penetration device 14. The bottom wall has a peripheral portion 23 and includes a central opening 24 for receiving the skin penetration device 14. This peripheral portion 23 of the bottom wall 18 surrounding the opening 24 forms a shelf 26 that extends beyond the receiving side wall 28, which is dimensioned to receive the skin penetrating device 14. Have.

  The skin penetration device 14 of the embodiment shown in FIGS. 1-6 has an array of microneedles. As best shown in FIG. 4, the skin penetration device 14 includes a base 30 having a substantially flat top surface 32 and a bottom surface 34. A plurality of isolated skin penetrating members 36 in the form of microneedles project downward from the bottom surface 34. As shown in FIGS. 4 and 5, the skin penetrating member 36 has a substantially cylindrical side wall 38 and an inclined tip 40. An axial passage 42 extends through each skin penetrating member 36 from the inclined tip 40 to the top surface 32 of the base 30. This axial passage 42 is in fluid communication with the cavity 22 of the housing 12. In a typical example, the skin penetrating members 36 extend vertically from the bottom surface 34 and are arranged in rows and columns separated from each other.

  In the preferred embodiment of the present invention, the skin penetration device 14 is coupled to the bottom wall 18 of the housing 12 such that the bottom wall 34 of the base 30 is flush with the bottom surface of the bottom wall 18 of the housing 12. In other words, the bottom surface 34 of the skin penetration device 14 is flush with the bottom wall 18 of the housing 12. As shown in FIG. 4, the opening 24 in the bottom wall 18 is slightly larger than the outer periphery of the skin penetrating device 14, forming a small gap between the outer periphery of the skin penetrating device and the receiving side wall 28. In a representative example, skin penetration device 14 is attached to bottom wall 18 by filling adhesive 46 with this gap. Preferably, this adhesive 46 having a viscosity capable of flowing into the gap 44 is heat treated to permanently secure the skin penetrating device 14 to the housing 12.

  As is apparent from FIG. 3, the skin penetration device 14 has a substantially square base 30 located in the center of the bottom wall 18 of the housing 12. In other embodiments, the base 30 of the skin penetrating device 14 may be generally circular or other shapes. Similarly, a circle is one of the preferred shapes for the housing 12. In other examples, the housing 12 may be substantially square or other rectangular or otherwise shaped.

  In the preferred embodiment, the housing 14 is pressurizable, which indicates that a sufficient amount of material has been delivered to the patient from the cavity 22 and provides a supply facilitating pressure during the delivery operation to provide the material. An elastically biased supply member 48 is provided for increasing the supply speed. The elastically biased supply member 48 moves to a position where a sufficient amount of material is supplied, and the presence of this member 48 at that position supplies a sufficient amount of material. Is displayed. In consideration of the display function, the elastically biased supply member 48 can be seen from the outside of the supply device 10. The top wall 16 includes a generally concave inner surface 50, a substantially projecting outer surface 52, and a mechanism for filling the cavity 22 with a substance to be delivered to the patient. In the illustrated embodiment, the mechanism includes a coupling member 54 having an inlet port 56 that forms a passage for the coupling member 54, and material from the cavity 22 through the inlet port 56 that permits introduction of material into the cavity 22. Is provided with a check valve 58 for prohibiting leakage of water. As another example, the mechanism can include a septum that is pierced by, for example, a syringe needle, which can reattach itself when the needle is removed. Other mechanisms can also be used.

  The elastically biased supply member 48 is an elastically inflatable member that is connected to the top wall 16 and closes the opening 60 in the top wall. In a preferred embodiment of the present invention, this elastically biased inflatable supply member 48 expands when the interior of the cavity 22 is pressurized and assumes a normal shape when the pressure is released. A diaphragm made of an elastic material that returns to its dimensions. The elastic material has an area, thickness, and elasticity that provides a supply pressure sufficient to supply a substance from the cavity 22 through the skin penetration device 14 to the patient. In moving from the pressurized position to the non-pressurized position, the elastically biased supply member 48 is equal to the volume of the cavity 22 when the elastically biased member is in its non-pressurized position. Move through the volume.

  In the illustrated embodiment, the elastically biased supply member 48 is substantially circular and is connected to the top wall 16. In other embodiments, the resiliently biased delivery member 48 can take other shapes depending on the delivery requirements of the device 10. Further, the supply member 48 may be coupled to the side wall. Suitable materials for delivery device 48 are natural rubber and synthetic rubbers such as polystyrene / butadiene copolymers. The elastic member 48 may be a separate member attached to the housing 12 with an appropriate adhesive, or may be formed integrally with the housing 12, and the housing 12 and the member 48 may be formed by a single molding. Made as a member. The housing 12 is made of a sturdy non-intumescent material.

  Device 10 has dimensions and shapes that are applied directly to the surface of the patient's skin so that skin penetration device 14 penetrates the skin to the desired depth. The device 10 comprises a flexible strip material 64 extending from both sides of the housing. The strip material 64 is preferably a flexible polymer film having an adhesive 66 on the bottom surface 68. The strip 64 has a width slightly smaller than the diameter of the housing 12 and a length sufficient to secure the housing 12 to the surface of the patient's skin. Typically, this adhesive 66 is a pressure sensitive adhesive.

  The device 10 is preferably configured as a disposable item that can be manufactured by a number of processes and used only once. The housing 12 is made from a polymeric material by an injection, vacuum or blow molding process. In the illustrated embodiment, the top wall 16, the bottom wall 18, and the side wall 20 are formed as one piece. In another example, the housing 12 forms a liquid-tight housing assembled by joining separate elements with an adhesive.

  Typically, the device 10 is manufactured and packaged in a sterilized state. The device 10 may be filled with the substance to be administered immediately before use, or may have been previously filled. A cover can be placed over the skin penetrating device 14 to protect and keep the device sterile during storage. A suitable release sheet (not shown) is provided on the adhesive layer 66. The release sheet and cover can be removed immediately before use.

  A method of delivering material into a patient's skin using the device 10 is illustrated in FIG. The device 10 is placed on the surface of the patient's skin 70 and pressed downward against the skin until the skin penetrating member 36 penetrates the skin. The penetration depth is determined by the length, width and spacing of the penetration member 36. Insufficient spacing between the skin penetrating members 36 increases the skin's resistance to penetration of the skin penetrating members. This phenomenon is also referred to as a “nail bed” because it allows light workers to lie on a nail bed that appears dangerous without serious injury. Preferably, the skin penetrating member 36 has dimensions and orientations that penetrate the surface of the skin 70 substantially evenly as shown in FIG. In the illustrated embodiment, the end of the strip 64 is connected to the side wall of the device 10 in a region at a slight distance from the bottom wall 18 of the housing 12. This configuration maintains a slight downward pressure of the housing 12 on the skin 70 when the strip 64 is attached to the skin 70 as shown in FIG. In another example, the strip material 64 is connected to the sidewall 20 at the bottom wall 18.

  As can be seen from FIGS. 5 and 6, the connecting member 56 is configured to be connected to the unit dose drug delivery device 72. For this purpose, the connection member 56 can comprise a Luer-type collar or a friction fit connection. The illustrated unit dose drug delivery device 72 has an outer housing 74, a hinged operating member 76, a luer connector that engages the coupling member 56 in a fluid-tight manner, and other configurations, as shown in FIG. A supply tip 78 is provided. The unit dose drug delivery device 72 also includes an inner bag (not shown) that is in fluid communication with the delivery tip 78. This unit dose drug delivery device 72 can be used to fill the device 10 with a pre-metered dose of drug delivered to the patient. As a result, if the elastically biased member 48 reaches the non-expanded / non-pressurized position again, it indicates that a pre-weighed dose of drug has been supplied. A suitable unit dose drug delivery device is commercially available from Becton Dickinson Company under the UNIJECT trademark. Other unit dose drug delivery devices can also be used.

  The device 10 is positioned over the patient's skin 70 as shown in FIG. 6 and a unit dose drug delivery device 72 is coupled to the coupling member 54. The operating member 76 is pushed inwardly to compress the inner bag of the unit dose drug delivery device 72 and inject the substance contained in the bag into the cavity 22 of the housing 12, as shown by the arrow 80 in FIG. To do. The material is injected with sufficient force to cause the elastically biased member 48 to expand outwardly from the top wall 16. Next, the unit dose drug delivery device 72 is removed from the coupling member 54 while the check valve 58 prevents the substance from escaping from the device 10 through the coupling member 56. The elasticity of the elastic biasing member 48 maintains the supply-promoting pressure in the cavity 22 and slowly pushes the substance through the axial passage 42 of the skin penetrating member 36 into the patient's skin where it is utilized by the body. Is done.

  The elastically biased member 48 returns to its original shape and dimensions as the material is supplied. The size and elasticity of the elastic biasing member 48 determines the volume of material that can be delivered and the rate at which the material is delivered to the patient. After a dose of material has been delivered to the patient, the resilient biasing member 48 returns to its original shape and size, thereby indicating that a sufficient amount of material has been delivered. The device 10 is then removed from the patient's skin and discarded.

  The housing 12 is preferably made of a plastic material that does not react with the substance delivered to the patient. Suitable plastic materials include polyethylene, polypropylene, polyester, polyamide, polycarbonate and copolymers thereof.

  The skin penetration device 14 can also be made of materials known to be suitable in the art. The skin penetrating member 36 may be a microneedle made of a silicon wafer that is machined or etched to form an array of microneedles. In another example, the skin penetrating member may be made of any of stainless steel, tungsten steel, any alloy of nickel, molybdenum, chromium, cobalt and titanium, and other non-reactive metals. In yet another example, the skin penetrating member may be made of a ceramic material, glass or polymer. In another embodiment, the skin penetration device 14 can be formed of different skin penetration members attached to a suitable base.

  The skin penetrating member 36 has a length suitable for obtaining a desired depth in the skin. The length and thickness of the skin penetrating member is selected based on the substance to be administered and the thickness of the skin where the device is applied. The skin penetrating member may be a micro needle, a micro tube, a solid or hollow needle, a lancet, or the like. Generally, skin penetrating member 36 has a length of about 50 microns to about 1500 microns, preferably about 500 microns to 1000 microns. In one embodiment, the skin penetrating member 36 comprises a needle of about 30 gauge to about 50 gauge mounted in a hole formed in the base. The skin penetrating member 36 is secured to the base 30 and extends outwardly therefrom to have an effective length of about 50 microns to 1500 microns. In addition to a circular cross-section, the skin penetrating member 36 can have a substantially square cross-sectional shape. As another example, the skin penetrating member 36 may have a triangular shape, a cylindrical shape, a pyramid shape, or a flat blade.

The array of skin penetrating members 36 has a width and length sufficient to accommodate the number and size of skin penetrating members 36 necessary to obtain the desired skin penetration depth and delivery or sampling rate. . If an array of skin penetrating member 36 is used, the area of the array is preferably from about ^{1cm 2 ~10cm} 2.

  In general, when the device is used as a delivery device, a drug or drug solution is introduced into port 56 by a syringe or other fluid delivery device. In another embodiment, a dried or lyophilized drug or agent is provided in the cavity 22 on the outer surface of the skin penetrating member 36 or in the axial passage 42 of the skin penetrating member. Next, a diluent such as distilled water or saline is injected into the cavity 22 to dissolve and reconstitute the drug or drug. Drugs and drugs are supplied to the patient through the micro needle.

  7A, 7B and 8 illustrate another embodiment of the delivery device 82. FIG. In this embodiment, the dispensing device 82 includes a housing 84 having a bottom wall 86 and a side wall 88. A skin penetration device 90 having a plurality of spaced skin penetration members 91 is connected to the bottom wall 86. An elastically biased top wall 92 is connected to the side wall 88 and separates from the bottom wall 86 to form an internal cavity 94. The skin penetrating member 91 can have all of the various shapes of the skin penetrating member 36 of the previous embodiment to supply a substance to the patient.

  The top wall 92 is made of an elastic material that can expand and expand the cavity 94 when a substance is introduced into the cavity 94 under pressure. As in the previous embodiment, the top wall 92 comprises a connecting member 96 having a passage and an internal check valve, which connecting member 96 is a unit dose drug infusion device 72 shown in FIGS. Etc. can be connected to a unit dose drug injection device. The bottom wall 86 and the side wall 88 are preferably made of a sturdy non-intumescent material.

  As in the previous embodiment, the dispensing device 82 comprises a flexible strip material 100 having an adhesive coding 102. In the illustrated embodiment, the strip material 100 is connected to a side wall 88 adjacent to the bottom wall 86 so that the bottom surface of the strip material 100 is flush with the bottom wall 86.

  The delivery device 82 is placed on the surface of the skin 106 and pressed downward to allow the needle 91 of the skin penetration member 90 to penetrate the skin to a selected depth. The strip material 100 is attached to the skin 106 with an adhesive and removably secures the device 82 in place. A unit dose drug injection device is then connected to the connecting member 96 and a fixed dose of drug is injected into the cavity 94 under sufficient pressure to inflate the top wall 92 outwardly as shown in FIG. . The elasticity of the ceiling wall 92 creates a supply pressure sufficient to supply the substance into the skin through the skin penetration device 90, where the substance is absorbed and utilized by the body. Returning the top wall to its original unexpanded position indicates that a sufficient amount of material has been delivered.

  9-11 illustrate another embodiment of the delivery device 110 of the present invention. The delivery device 110 includes a housing 112 having a top surface 114, a bottom surface 118 that forms a recess 118, and an internal cavity 120 that opens downward. The recess 118 is formed by a peripheral wall 124 and a shelf 122 for receiving the skin penetration device 126.

  The skin penetrating device 126 includes a base 128 having a plurality of skin penetrating members 130 such as microneedles, each penetrating member extending outwardly from the bottom surface 132 of the base 128 with an axial passage. The skin penetrating member 130 may be formed integrally with the base 128 as in the above-described embodiment. Alternatively, the skin penetrating member 130 may be a separate element fixed to each hole of the base 128. The base 128 has a thickness corresponding to the depth of the peripheral wall 124, and the bottom surface 132 of the base is flush with the bottom surface 116 of the housing 112.

  As is apparent from FIGS. 10 and 11, the bottom surface 116 has an area that is larger than the area of the skin penetrating device 126 and provides a margin for surrounding the skin penetrating device 126. In order to attach the delivery device 110 to the patient's skin, a pressure sensitive adhesive 136 is provided at the margin of the bottom surface 116. Preferably, the pressure sensitive adhesive 136 forms a continuous closed loop that surrounds the skin penetrating device 126 and forms a seal around the skin supply area that the skin penetrating device 126 is in contact with.

  As is apparent from FIGS. 9 and 11, a collar 138 having a central passage 140 communicating with the cavity 120 projects above the top surface 114 of the housing 112. A check valve 142 and a connecting member 144 are provided on the collar 138. An opening 146 in the top surface 114 is closed by an elastically biased member 148 connected to the housing 112 to seal the cavity 120. The expansion position of the elastic biasing member 148 is shown by a dotted line in FIG. The elastic biasing member 148 is preferably made of an elastomer that can be expanded and deformed outwardly from the housing 112 to generate an internal supply facilitating pressure to assist in delivering material from the cavity 120 through the needle 130 to the patient.

  The delivery device 110 of the embodiment of FIGS. 9-11 has a relatively thin profile and a small volume cavity 120. This small volume reduces dead space and can reduce the amount of material remaining in the housing 112 after the material is delivered to the patient. In a representative example, the housing 112 is made of a polymeric material that is sufficiently flexible to conform to the shape of the patient's skin.

  The delivery device 110 is placed on the surface of the patient's skin 150 and is pressed downward to cause a skin penetration member 130 such as a microneedle to penetrate the skin. The substance to be delivered to the patient is introduced with sufficient pressure through the coupling member 144 and the central passage 140 into the cavity 120, causing the delivery member 148 to expand as shown by the dotted line in FIG. The substance to be delivered to the patient is introduced into the cavity 120 from the unit dose drug infusion device 72 or 98 as in the previous embodiment, or from a syringe, drug infusion pump, or other delivery device. When a sufficient amount of material is contained in the cavity 120, the delivery device is then separated from the connecting member 144. The supply member 148 generates a supply-enhancing pressure sufficient to deliver the substance through the skin penetrating member 130 to the patient's skin. As material is dispensed, supply member 148 moves toward its unexpanded position, indicating that a sufficient amount of material has been delivered. Once the substance has been delivered to the patient, the device 110 is peeled away from the skin surface and discarded.

  12-14 illustrate another embodiment of a delivery device 152 according to the present invention. The delivery device 152 includes a housing 154, an inflatable delivery member 156, and a skin penetration device 158.

  The housing 154 is a substantially circular member having a thin, flat profile and has a central hole 160 having an upper shelf 162 adjacent to the top surface 164. As shown in FIG. 14, an elastically biased member 156 is connected to the upper shelf 162 to close the upper end of the hole 160.

  The housing 154 also includes a lower shelf 166 on the bottom surface 168 surrounding the lower end of the hole 160. The lower shelf 166 forms a recess for receiving and mounting the skin penetration device 158 in the housing 154. As shown in FIG. 14, the supply member 156 and the skin penetration device 158 are spaced apart from each other to form an internal cavity 170 with the housing 154.

  The housing 154 includes a connecting member 172 that extends from a side surface of the housing 154 and is substantially flush with the housing. The collar 172 includes an inlet port 176 that defines an axial interior passage extending into the interior cavity 170, a check valve 178, and a coupling member 180 for coupling to a delivery device. The axial passage of the port 176 extends from the connecting member 180 through the side 174 of the housing 154 and communicates with the internal cavity 170.

  The bottom surface 168 of the housing 154 has an area that is larger than the area of the skin penetration device 158. A pressure sensitive adhesive forming a continuous closed loop is applied to the bottom margin 168 and surrounds the skin penetration device 158. Preferably, an adhesive 182 is applied to the margin 168 to cover a sufficient surface area and attach the device 152 to the patient's skin surface.

  The resilient biasing member 156 is preferably an inflatable member made of an elastomeric material. In the illustrated embodiment, the resilient biasing member 156 is a resilient diaphragm member 184 that expands outward from the housing 154 when a substance is introduced into the cavity 170 under pressure. Due to the elastic properties of the diaphragm member 184, a sufficient supply promoting pressure is generated inside the cavity 170.

  Similar to the previous embodiment, the skin penetration device 158 includes a base 186 having a skin penetration member 188 such as a plurality of microneedles spaced apart from each other. The method of delivering material into the patient's skin using the device 152 is apparent from FIG. The delivery device 152 is placed on the patient's skin 170 and pressed downward, the skin penetrating member 188 penetrates the skin 190, and the adhesive 182 contacts the skin 190 with sufficient force, causing the device 152 to touch the skin. Attach and form a continuous seal between the device and the skin, surrounding the entire circumference of the skin penetration device 158. A unit dose drug infusion device, such as the infusion device 72, is connected to the coupling member 180 to introduce a substance into the cavity 170 under sufficient pressure to expand the supply member 184 outward as shown by the dotted line in FIG. . The unit dose drug infusion device is removed after the cavity 170 is filled. The delivery device 152 remains in contact with the skin 190 for a time sufficient for the delivery member 184 to deliver material from the cavity 170 through the skin penetration member 188 into the patient's skin. By reaching the non-expanded position again, the elastic biasing member 156 indicates that a sufficient amount of material has been supplied. The delivery device 152 is then separated from the skin 190 and discarded.

  While various embodiments have been selected to describe the present invention, it is understood that one skilled in the art can make various additions and modifications without departing from the scope of the invention as defined in the claims. Should be recognized.

It is a top view of the supply device which concerns on 1st Embodiment of this invention. FIG. 2 is a front view of the device of FIG. 1. FIG. 2 is a bottom view of the device of FIG. 1 showing a skin penetration device. FIG. 3 is an enlarged partial cross-sectional view of the device of FIG. 2 showing the skin penetration device 3 joined to the housing. Fig. 5 is an enlarged cross-sectional view taken along line 5-5 of Fig. 1 showing the housing cavity and the normal and relaxed diaphragms. FIG. 6 is a cross-sectional view similar to FIG. 5 but showing a diaphragm in a stretched state that is an indicator that the material is sufficiently filled in the cavity and that the supply acceleration pressure is also sufficient. FIG. 7A is a cross-sectional side view of a delivery device according to a second embodiment of the present invention, the device having an inflatable diaphragm forming a top wall. FIG. 7B is a top view of the device of FIG. 7A. FIG. 7B is a side sectional view similar to FIG. 7A, but with the cavity filled with material and the diaphragm in a stretched state. FIG. 6 is a top view of a delivery device of a third embodiment of the present invention, showing a ceiling wall inlet port and an inflatable diaphragm. FIG. 10 is a bottom view of the supply device of FIG. 9. FIG. 10 is an enlarged cross-sectional view taken along line 11-11 in FIG. FIG. 10 is a top view of a supply device according to a fourth embodiment of the present invention, showing an inflatable top wall and an inlet port connected to the side of the housing. FIG. 13 is a bottom view of the device of FIG. 12, showing a microneedle array. FIG. 14 is an enlarged cross-sectional view taken along line 14-14 of FIG. 12, showing a microneedle array and an internal chamber.

Claims (45)

An intradermal delivery device for delivering a substance to a patient,
A housing having an internal cavity dimensioned to receive a substance for delivery to a patient;
A skin penetration device in fluid communication with the cavity;
An indicator indicating that a sufficient amount of material has been supplied to the patient;
Intradermal supply device with.   The indicator comprises an indicator member having at least one portion movable to a position where a sufficient amount of substance has been supplied, and that the indicator member is in the position so that a sufficient amount of substance has been supplied. The intradermal delivery device of claim 1 as shown.   The intradermal supply device according to claim 2, wherein when the movable part of the indicator member is in the position, the movable part is visible from the outside of the intradermal supply device.   The intradermal delivery device of claim 2, wherein the movable part is elastically biased toward the position.   The intradermal supply device according to claim 4, wherein the indicator member includes an elastic member that can expand from the position, and the elasticity of the expandable elastic member biases the movable part toward the position.   6. The intradermal delivery device of claim 5, wherein the elasticity of the expandable elastic member comprises means for generating a supply pressure against the material in the cavity until a sufficient amount of material is supplied.   The intradermal delivery device of claim 6, wherein the expandable member is expandable by introducing a substance into the cavity under pressure.   A sufficient amount of material to be supplied forms a single volume, the indicator member moves through the single volume, and the volume through which the indicator member passes is the volume of the material to be supplied. The intradermal delivery device of claim 2, wherein the intradermal delivery device is at least equal to the volume.   The intradermal delivery device of claim 1, wherein the housing further comprises an inlet for the substance into the cavity.   The intradermal delivery device of claim 9, further comprising a check valve connected to the inlet to prevent the material from exiting the cavity through the inlet.   The intradermal delivery device of claim 5, wherein the inflatable elastic member is integral with the housing.   The intradermal delivery device of claim 11, wherein the expandable elastic member is made of an elastomeric material.   6. The intradermal delivery device of claim 5, wherein the housing comprises a top wall and the inflatable elastic member is connected to the top wall.   14. The intradermal delivery device of claim 13, wherein the top wall includes an opening and the inflatable elastic member closes the opening.   The intradermal delivery device of claim 5, wherein the expandable elastic member is a diaphragm.   The intradermal delivery device of claim 15, wherein the diaphragm is made of an elastomeric material.   The intradermal delivery device of claim 15, wherein the inflatable elastic member forms a top wall of the housing.   18. The intradermal delivery device of claim 17, further comprising an inlet for entering material into the cavity.   The intradermal delivery device of claim 1, further comprising an attachment mechanism for attaching the device to the surface of the skin.   14. The intradermal delivery device of claim 13, wherein the attachment mechanism comprises an adhesive that removably joins the device to the skin.   The intradermal delivery device of claim 1, wherein the skin penetration device comprises a skin penetration member having a length of about 50 microns to about 1500 microns.   The intradermal delivery device of claim 21, wherein the skin penetration device comprises a plurality of the skin penetration members.   The intradermal delivery device of claim 21, wherein the skin penetration device is a needle of about 30 gauge to about 50 gauge.   The intradermal delivery device of claim 1, wherein the skin penetration device comprises a skin penetration member having a length of about 500 microns to about 1000 microns.   25. The intradermal delivery device of claim 24, wherein the skin penetration device comprises a plurality of the skin penetration members.   25. The intradermal delivery device of claim 24, wherein the skin penetrating member is a needle of about 30 gauge to about 50 gauge.   6. The intradermal delivery device of claim 5, wherein the inflatable elastic member comprises at least a portion of an internal cavity sized to receive a substance to be delivered to a patient.   28. The intradermal delivery device of claim 27, wherein the housing has a substantially non-inflatable portion made of a substantially non-inflatable material.   29. The intradermal delivery device of claim 28, wherein the substantially unexpanded portion comprises an inlet for supplying the material to the cavity.   30. The intradermal delivery device of claim 29, further comprising a check valve connected to the inlet to prevent material from exiting the cavity through the inlet.   The intradermal delivery device of claim 1, further comprising a flexible adhesive coat member coupled to the housing, wherein the device is adhesively attached to the patient's skin.   32. The intradermal delivery device of claim 31, wherein the adhesive coat member is a band.   The intradermal delivery device of claim 1, wherein the skin penetrating member is a needle having an axial passage in fluid communication with the cavity for delivering the substance to the patient.   The intradermal delivery device of claim 1, further comprising means for liquid-tightly transferring the substance from a substance source to the cavity.   35. The intradermal delivery device of claim 34, wherein the moving means comprises an inlet opening in the housing and a mechanism for removably connecting the liquid source to the housing.   35. The intradermal delivery device of claim 34, wherein the liquid source is a unit dose drug delivery device.   35. The intradermal delivery device of claim 34, wherein the inflatable elastic diaphragm forms an outer wall of the housing.   38. The intradermal delivery device of claim 37, wherein the outer wall is at the end of a skin penetration device.   The intradermal delivery device of claim 1, wherein the housing has a bottom to which the skin penetration device is coupled.   The intradermal delivery device of claim 1, wherein the indicator member comprises at least a portion of the internal cavity dimensioned to receive a substance for delivery to a patient. An intradermal delivery device for delivering a substance to a patient,
A housing having an internal cavity dimensioned to receive a substance for delivery to a patient;
A skin penetration device in fluid communication with the cavity;
Means to indicate that a sufficient amount of material has been supplied to the patient;
Intradermal supply device with. A method of supplying a substance into a patient's skin,
Providing a supply device having a housing with an internal cavity and a skin penetration device in fluid communication with the cavity to pressurize the housing to maintain the supply pressure within the cavity;
Positioning the delivery device in a target area on the patient's skin and applying sufficient force to cause the skin penetration device to penetrate the patient's skin;
Introducing a substance under pressure into the cavity of the housing;
Generating the supply pressure in the cavity using the introduction pressure;
A method of supplying the substance to the patient.   Providing the skin penetrating device with at least one microneedle having a length of about 50 microns to about 1500 microns in the step of providing the device, and penetrating the microneedles into the skin in the penetrating step. Item 42. The method according to Item 42.   In the step of providing the device, an inflatable elastic member is provided in the supply device, and in the introducing step, the substance is introduced into the cavity with a force sufficient to expand the inflatable elastic member. 43. The method of claim 42, wherein the delivery pressure is generated within and the substance is delivered to the patient.   45. The method of claim 44, wherein the inflatable elastic member is a diaphragm made of an elastomeric material.

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